The lysis of hemostatic blood clots is orchestrated by a complex array of biochemical pathways and regulated to allow the clot to disappear as a wound heals. If a clot dissolves too quickly, the wound may rebleed. The study of fibrinolysis has traditionally focused on blood obtained by atraumatic venipuncture, although such samples lack any components that might be contributed by the extravascular tissue, which is where hemostatic clots naturally exist. Therefore, we have compared the in vitro lysis rate of blood obtained by venipuncture and blood obtained by fingerstick, which passes through extravascular tissue in the process of bleeding. Clots are incubated for 2-48 hours, and their degradation is monitored by measuring proteolytic breakdown products in the serum. We have found that fingerstick clots lyse significantly faster than clots of venipuncture blood. We have assayed fingerstick and venipuncture samples for all the proteins known to be involved in fibrinolysis but have not found significant differences between the two. With the hypothesis that matrix metalloproteinases (MMPs) might be contributing to the lysis of fingerstick clots, we have added inhibitors of these enzymes to the blood samples when they are first obtained. The inhibitors change the lytic rate of fingerstick clots in different ways but have no obvious effect on the lysis of venipuncture clots. We will pursue this line of evidence by assaying samples for specific MMPs. If we can identify specific enzymes or inhibitors that are operative in fingerstick blood, we will look for abnormalities in these proteins in patients with undiagnosed bleeding disorders.